title: Hemospan improves outcome in a model of perioperative hemodilution and blood loss in the rat: comparison with hydroxyethyl starch.
abstract: OBJECTIVE
  Hemospan (Sangart Inc, San Diego, CA) (MP4) is a hemoglobin-based oxygen carrier consisting of human hemoglobin modified with polyethylene glycol. This study evaluated the effects of MP4 on blood volume, hemodynamics, and metabolic stability in a rat model of hemodilution and hemorrhage. MP4 was compared with hydroxyethyl starch solutions of differing concentrations (ie, HES 260/0.45 and HES 130/0.4).
  
  
  METHODS
  An open-label, randomized comparison of treatments.
  
  
  METHODS
  Pharmaceutical industry.
  
  
  METHODS
  Sprague Dawley rats.
  
  
  METHODS
  Rats underwent 50% hemodilution with one of the solutions. Control rats were not hemodiluted. Blood volume was determined at baseline and 0, 60, and 120 minutes after exchange. In separate groups, hemodilution and subsequent 60% hemorrhage were examined to determine effectiveness of hemodilution.
  
  
  RESULTS
  Endpoints were blood volume after hemodilution and survival, hemodynamics, and acid-base status during hemorrhage. Volume expansion was similar with MP4 (159% of infused volume) and HES 260/0.45 (145%) and less with HES 130/0.4 (104%). The duration of expansion was longest with MP4 (1-2 hours). In the hemorrhage studies, 2-hour survival was 90% with MP4, 50% with controls, and 10% and 0% with HES 260/0.45 and HES 130/0.4, respectively. The severity of hemodynamic and acid-base changes paralleled the survival, with the least disturbance observed in MP4-treated animals.
  
  
  CONCLUSIONS
  Hemodilution with MP4 was more effective in maintaining hemodynamic and metabolic stability than starch solutions or no hemodilution before simulated intraoperative hemorrhage. The benefit of MP4 is not ascribed solely to volume expansion. The results suggest that perioperative administration of MP4 may improve outcomes in surgical settings.
authors.affiliation: Sangart Inc, San Diego, CA 92121, USA. myoung@sangart.com
authors.forename: Mark A
authors.initials: MA
authors.lastname: Young
authors.forename: Jeff
authors.initials: J
authors.lastname: Lohman
authors.forename: Ashok
authors.initials: A
authors.lastname: Malavalli
authors.forename: Kim D
authors.initials: KD
authors.lastname: Vandegriff
authors.forename: Robert M
authors.initials: RM
authors.lastname: Winslow
mesh_terms: D000818:Animals; D001802:Blood Substitutes / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006438:Hemodilution / Q000379:methods*; D006454:Hemoglobins / Q000627:therapeutic use*; D006801:Humans; D006895:Hydroxyethyl Starch Derivatives / Q000627:therapeutic use*; D008297:Male; D008301:Maleimides / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D019106:Postoperative Hemorrhage / Q000188:drug therapy* / Q000209:etiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome
chemical_list: D001802:Blood Substitutes; D006454:Hemoglobins; D006895:Hydroxyethyl Starch Derivatives; D008301:Maleimides; C493836:maleimide-polyethylene glycol-modified hemoglobin, MP4; D011092:Polyethylene Glycols